Search

Ischemic stroke (IS) greatly threatens human health resulting in high mortality and substantial loss of function. Recent studies have shown that the outcome of IS has sex specific, but its mechanism is still unclear. This study is aimed at identifying the sexually dimorphic to peripheral immune response in IS progression, predicting potential prognostic biomarkers that can lead to sex-specific outcome, and revealing potential treatment targets. Gene expression dataset GSE37587, including 68 peripheral whole blood samples which were collected within 24 hours from known onset of symptom and again at 24-48 hours after onset (20 women and 14 men), was downloaded from the Gene Expression Omnibus (GEO) datasets. First, using Bioconductor R package, two kinds of differentially expressed genes (DEGs) (nonsex-specific- and sex-specific-DEGs) were screened by follow-up (24-48 hours) vs. baseline (24 hours). 30 nonsex-specific DEGs (1 upregulated and 29 downregulated), 79 female-specific DEGs (25 upregulated and 54 downregulated), and none of male-specific DEGs were obtained finally. Second, bioinformatics analysis of female-specific DEGs was performed. Gene Ontology (GO) functional annotation analysis shows that DEGs were mainly enriched in translational initiation, cytosolic ribosome, and structural constituent of ribosome. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that the top 6 enrichment pathways are ribosome, nuclear factor-­kappa B (NF-kappa B) signaling pathway, apoptosis, mineral absorption, nonalcoholic fatty liver disease, and pertussis. Three functional modules were clustered in the protein–protein interaction (PPI) network of DEGs. The top 10 key genes of the PPI network constructed were selected, including RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2. Sex difference of ribosome in stroke-induced peripheral immunosuppression may be the potential mechanism of sex disparities in outcome after IS, and women are more likely to have stroke-induced immunosuppression. RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2 may be novel prognostic biomarkers and potential therapeutic targets for IS.

Highlights • Dysregulated and excessive cytokine storm is essential for critically ill COVID-19 development. • Mechanisms of SARS-CoV-2-infected included ACE2 receptor-mediated inflammatory response, Cell Pyroptosis, Delayed IFN-α and -β response, and Anti-S-IgG-mediated inflammatory response. • Infected lung epithelial cells and macrophages mainly release cytokines involved in innate immunity and adaptive immunity. • Endothelial cells damage and microvascular thrombosis played an important role in pathophysiological changes of COVID-19 involved respiratory failure, hypotension, liver and kidney injury. • Individualized targeted cytokine drug therapy might an effective measure to alleviate the violent inflammation besides Remdesivir, Chloroquine, Lopinavir and Ritonavir, Favipiravir etc., A novel coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading globally, causing severe pneumonia and acute lung injury in many patients. Even worse, severe respiratory may develop into acute respiratory distress syndrome and multiple organ dysfunction syndrome in COVID-19. The cytokine storm caused by immune over-activation due to virus infection may be an important cause of death in the late period of progress, but the pathogenesis of cytokine storm is still unclear. This article reviews the mechanisms of SARS-CoV-2-induced cytokine storm in detail based on the current discovered researches, and put forward some valuable medication ideas for the targeted cytokines drug researches and treatment. The goal of this work will be helpful for reducing excessive immune response.

Background As the mechanism of systemic inflammatory response in the course of cancer progression is gradually revealed, research has begun to focus on the two indictors of neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) which may be associated with clinical disease development, treatment, and prognosis in patients who are undergoing surgery, chemotherapy, targeted therapy, and immunotherapy. We aim to define the clinical application values of those two biomarkers in multiple cancers. Methods PubMed and Web of Science are used to perform the systematic literature research. Related articles and references were identified for analyzing the association of between NLR and PLR with treatment outcome, as well as progression of cancers. Results NLR and PLR are convenient, easy to calculate, economical, and practical biomarkers, effectively predicting treatment outcome and risk of death based on inflammatory cells. Elevated NLR and PLR are significantly in line with worse clinical pathological characteristics, deeper invasiveness, more lymph node metastasis and advanced TNM stage. A significant association was observed that high NLR and PLR predict poor overall survival and disease-free survival. Conclusions NLR and PLR can be used as available biomarkers in prognostic survival and formulation of treatment strategy of multiple cancers.

RNA binding proteins (RBPs) dysregulation have been reported in various malignant tumors and associated with the occurrence and development of cancer. However, the role of RBPs in lung adenocarcinoma (LUAD) is poorly understood. We downloaded the RNA sequencing data of LUAD from the Cancer Genome Atlas (TCGA) database and determined the differently expressed RBPs between normal and cancer tissues. The study then systemically investigated the expression and prognostic value of these RBPs by a series of bioinformatics analysis. A total of 223 differently expressed RBPs were identified, including 101 up-regulated and 122 down-regulated RBPs. Eight RBPs (IGF2BP1, IFIT1B, PABPC1, TLR8, GAPDH, PIWIL4, RNPC3, and ZC3H12C) were identified as prognosis related hub gene and used to construct a prognostic model. Further analysis indicated that the patients in the high-risk subgroup had poor overall survival(OS) compared to those in low-risk subgroup based on the model. The area under the curve of the time-dependent receiver operator characteristic curve of the prognostic model are 0.775 in TCGA cohort and 0.814 in GSE31210 cohort, confirming a good prognostic model. We also established a nomogram based on eight RBPs mRNA and internal validation in the TCGA cohort, which displayed a favorable discriminating ability for lung adenocarcinoma.

To evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer.Primary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated.The BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673±2.143, and clinical-sensitive group -1.436±2.594 (P=0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529±1.982 and clinical-sensitive group -3.188±2.601 (P=0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P=0.074), and the TUBB3 expressions between the two groups were also not significantly different (P=0.619). When the intercept point value BRCA1 mRNA expression logarithm was -0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively.BRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer.

To predict clinical chemotherapy sensitivity of primary ovarian cancer by jointing adenosine triphosphate (ATP)-tumor chemo-sensitivity assay (TCA) method in vitro and detection of drug resistance genes, provide reference for clinical treatment.Forty-seven primary epithelial ovarian tumor samples were collected from the patients who received cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissue were tested for their sensitivity to carboplatin (CBP), cisplatin (DDP), paclitaxel (PTX) and CBP + PTX using ATP-TCA method in vitro; at same time, real-time quantitative PCR was used to analysis BRCA1 and ERCC1 mRNA relative expression in forty-six specimens (1 frozen tumor samples mRNA were not detected due to serious degradation). The relationship between ATP-TCA test results, clinical indicators, and the effectiveness of the joint prediction on clinical chemo-sensitivity by combining these two methods were statistically analyzed using chi-square test.(1) The results showns that three programs of DDP, CBP and PTX + CBP were significantly related with clinical results (P0.05) in vitro, in which the compliance rate in PTX + CBP program was the highest 83% (39/47), and the predictive sensitivity, predictive specificity, positive predictive value, negative predictive value and predictive accurate rate were 90%, 71%, 84% and 80%, respectively. PTX + CBP combined in vitro test results was also related with residual tumor size and neoadjuvant chemotherapy, which was more prone to drug resistance with residual tumor larger than 2 cm (P = 0.023) and with neoadjuvant chemotherapy (P = 0.011). (2) BRCA1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was 0.673 ± 2.143 and -1.436 ± 2.594 (P = 0.008), ERCC1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was -0.529 ± 1.982 and -3.188 ± 2.601 (P = 0.001). There were also significant correlation among the expression levels of BRCA1, ERCC1 mRNA and clinical efficacy (P0.01). (3) ATP-TCA and detection of drug resistance genes combined to predict the clinical application of PTX + CBP resistance may occur in 8/9 cases.ATP-TCA may be an ideal method of in vitro drug sensitivity testing method, which could effectively predict clinical chemotherapy sensitivity. Combination of the drug-resistant associated genes detection method and the ATP-TCA method can increase the predictive effectiveness of ovarian cancer chemosensitivity and guide individual chemotherapy of ovarian cancer.

To explore the value of adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in individualized treatment of recurrent epithelial ovarian cancer (REOC), and to evaluate the correlation between the in vitro chemosensitivity assay and clinical drug sensitivity.Sixty-nine REOC specimens were tested by ATP-TCA assay retrospectively. The patients were divided into strong sensitive, moderate sensitively and resistant groups according to the ATP-TCA assay results. The clinical results were evaluated according to imaging and serum CA125 analysis. The correlation between in vitro ATP-TCA assay and clinical outcome was statistically analyzed by χ(2) test. The progression free survival (PFS) and overall survival (OS) of each group were analyzed using Kaplan-Meier method.The results of ATP-TCA assay had significant correlation with clinical outcome. The clinical chemotherapy outcome became better with increased drug sensitivity in vitro (χ(2) = 9.066, P = 0.004). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate for ATP-TCA method to predict the clinical chemotherapy sensitivity of REOC were 87.5%, 45.9%, 58.3%, 80.9% and 65.2%, respectively. The mean PFS of strong sensitive group, moderately sensitive group and resistant group were 187.1 days, 195.0 days and 60.3 days, respectively. The mean OS were 476.7, 335.7 and 237.5 days, respectively, following the start of TCA-directed therapy. The PFS and OS of the two sensitivity groups in vitro were significantly longer than that of the in vitro-resistant group (P0.01).The results of ATP-TCA assay are well correlated with clinical treatment responses. The assay may be an important and useful method for individualized chemotherapy for recurrent ovarian cancer.

Objective The objective of the study was to investigate the expression and regulation of polycomb group (PcG) proteins in human neural tube defects (NTDs). Study Design PcG proteins in human NTD fetuses and age-matched controls were detected by Western blot. The relation between PcG proteins and microribonucleic acids was predicted and confirmed by the bioinformatics method, real-time polymerase chain reaction (PCR), dual-luciferase activity assay, and Western blot. The trimethyl condition of histone H3 Lys27 (H3K27) was detected by immunohistochemical and immunofluorescence. Results Embryonic ectoderm development protein (EED) was differentially detected in placenta, cerebral cortex, and spinal cord from NTDs and age-matched controls. MiR-30b can interact with 3'-untranslated region (UTR) of Eed and regulate endogenous EED expression in neural tissues. In addition, we found an inverse relationship between the miR-30b expression and the amount of trimethyl H3K27. Conclusion Differential expression of EED exists in the nerves system in human NTDs and that is regulated by miR-30b.

MicroRNAs (miRNAs) are small noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell growth. Although many microRNAs were found to express in central nervous system (CNS), the role of the regulatory networks in which they are involved and their function in the pathological process of nerve cells are only just emerging. In the present study, the possible mechanisms by which one neuronal miRNAs, miR-125b, affected the growth of nervous cells were investigated using in vitro cell line model.The expression pattern of miR-125b in ATRA-treated human glioma cell lines was detected by Northern blotting and in situ localization. The effect of miR-125b on the proliferation and apoptosis of human glioma cells was analyzed by MTS assay, TUNEL and Flow cytometry analysis. In addition, the identification of target gene of miR-125b was studied by dual-luciferase activity assay and Immunoblot Analysis.We found differential expression of miR-125b in 1.0 microM all-trans-retinoic acid (ATRA)-treated human glioma cell lines. Up-regulation of miR-125b partially restored cell viability and inhibited cell apoptosis in U343 cells treated by ATRA. Down-regulation of miR-125b decreased human glioma cells proliferation and enhanced the sensitivity of human glioma cells to ATRA-induced apoptosis. In addition, we found an inverse relationship between the expression of miR-125b and the cell apoptosis-related protein Bcl-2 modifying factor (Bmf), and miR-125b can interact with 3'-untranslated region (UTR) of Bmf.These findings indicate that overexpression of miR-125b promotes human glioma cell proliferation and inhibits ATRA-induced cell apoptosis and low expression of miR-125b sensitizes cells to ATRA-induced apoptosis. BMF may play an important role in the process of miR-125b influencing cell apoptosis.